Skip to main content
SpringerLink
Log in

The Association of Plasminogen Activator Inhibitor Type 1 (PAI-1) Level and PAI-1 4G/5G Gene Polymorphism with the Formation and the Grade of Endometrial Cancer

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor (Serpine 1), and it inhibits both tissue plasminogen activator and urokinase plasminogen activator which are important in fibrinolysis. We aimed to find whether there is a possible association between PAI-1 level, PAI-1 4G/5G polymorphism, and endometrial cancer. PAI-1 levels in peripheral blood were determined in 82 patients with endometrial carcinoma and 76 female healthy controls using an enzyme-linked immunoassay (ELISA). Then, the genomic DNA was extracted and screened by reverse hybridization procedure (Strip assay) to detect PAI 1 4G/5G polymorphism. The levels of PAI-1 in the patients were higher statistically in comparison to controls (P < 0.001). The distribution of PAI-1 4G/5G polymorphism was quite different between patients and controls (P = 0.008), and 4G allelic frequency was significantly higher in the patients of endometrial cancer than in controls (P = 0.026). We found significant difference between Grade 1 and Grade 2+3 patients in terms of the PAI-1 levels (P = 0.047). There was no association between PAI-1 4G/5G polymorphism and the grades of endometrial cancer (P = 0.993). Our data suggest that the level of PAI-1 and PAI-1 4G/5G gene polymorphism are effective in the formation of endometrial cancer. PAI-1 levels are also associated with the grades of endometrial cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abd El-Aziz TA, Rezk NA (2015) Relation of PAI-1 and TPA genes polymorphisms to acute myocardial infarction and its outcomes in Egyptian patients. Cell Biochem Biophys 71:227–234

    Article  PubMed  Google Scholar 

  • Al-Horani RA, Karuturi R, White DT, Desai UR (2015) Plasmin regulation through allosteric, sulfated, small molecules. Molecules 20:608–624

    Article  PubMed  Google Scholar 

  • Bogani G, Dowdy SC, Cliby WA, Ghezzi F, Diego Rossetti D, Mariani A (2014) Role of pelvic and para-aortic lymphadenectomy in endometrial cancer: current evidence. J Obstet Gynaecol Res 40:301–311

    Article  PubMed  PubMed Central  Google Scholar 

  • Castelló R, España F, Vázquez C, Fuster C, Almenar SM, Aznar J et al (2006) Plasminogen activator inhibitor-1 4G/5G polymorphism in breast cancer patients and its association with tissue PAI-1 levels and tumor severity. Thromb Res 117:487–492

    Article  PubMed  Google Scholar 

  • Dejouvencel T, Doeuvre L, Lacroix R, Plawinski L, Dignat-George F, Lijnen HR et al (2010) Fibrinolytic cross-talk: a new mechanism for plasmin formation. Blood 115:2048–2056

    Article  CAS  PubMed  Google Scholar 

  • Divella R, Daniele A, Abbate I, Savino E, Casamassima P, Sciortino G et al (2015) Circulating levels of PAI-1 and SERPINE1 4G/4G polymorphism are predictive of poor prognosis in HCC patients undergoing TACE. Transl Oncol 8:273–278

    Article  PubMed  PubMed Central  Google Scholar 

  • Dossenbach-Glaninger A, van Trotsenburg M, Dossenbach M, Oberkanins C, Moritz A, Krugluger W et al (2003) Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: impaired fibrinolysis and early pregnancy loss. Clin Chem 49:1081–1086

    Article  CAS  PubMed  Google Scholar 

  • Drinane MC, Sherman JA, Hall AE, Simons M, Mulligan-Kehoe MJ (2006) Plasminogen and plasmin activity in patients with coronary artery disease. J Thromb Haemost 4:1288–1295

    Article  CAS  PubMed  Google Scholar 

  • Fredstorp-Lidebring M, Bendahl PO, Brünner N, Casslén B, Högberg T, Långström-Einarsson E et al (2001) Urokinase plasminogen activator and its inhibitor, PAI-1, in association with progression-free survival in early stage endometrial cancer. Eur J Cancer 37:2339–2348

    Article  CAS  PubMed  Google Scholar 

  • Gilabert-Estellés J, Ramón LA, Braza-Boïls A, Gilabert J, Chirivella M, España F et al (2012) Plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G polymorphism and endometrial cancer. Influence of PAI-1 polymorphism on tissue PAI-1 antigen and mRNA expression and tumor severity. Thromb Res 130:242–247

    Article  PubMed  Google Scholar 

  • Gouri A, Dekaken A, El Bairi K, Aissaoui A, Laabed N, Chefrour M, Ciccolini J, Milano G, Benharkat S (2016) Plasminogen activator system and breast cancer: potential role in therapy decision making and precision medicine. Biomark Insights 11:105–111

    Article  PubMed  PubMed Central  Google Scholar 

  • Han T, Zhang G, Yan D, Yang H, Ma T, Ye Z (2016) Modulation of plasminogen activator inhibitor-1 (PAI-1) by the naphthoquinone shikonin. Fitoterapia 113:117–122

    Article  CAS  PubMed  Google Scholar 

  • Hosokawa K, Ohnishi-Wada T, Sameshima-Kaneko H, Nagasato T, Miura N, Kikuchi K, Koide T, Maruyama I, Urano T (2016) Plasminogen activator inhibitor type 1 in platelets induces thrombogenicity by increasing thrombolysis resistance under shear stress in an in vitro flow chamber model. Thromb Res 146:69–75

    Article  CAS  PubMed  Google Scholar 

  • Köhler U, Hiller K, Martin R, Langanke D, Naumann G, Bilek K et al (1997) Tumor-associated proteolytic factors uPA and PAI-1 in endometrial carcinoma. Gynecol Oncol 66:268–274

    Article  PubMed  Google Scholar 

  • Liguori R, Quaranta S, Di Fiore R, Elce A, Castaldo G, Amato F (2014) A novel polymorphism in the PAI-1 gene promoter enhances gene expression. a novel pro-thrombotic risk factor? Thromb Res 134:1229–1233

    Article  CAS  PubMed  Google Scholar 

  • McMahon BJ, Kwaan HC (2015) Components of the plasminogen-plasmin system as biologic markers for cancer. Adv Exp Med Biol 867:145–156

    Article  CAS  PubMed  Google Scholar 

  • Meyer LA, Bohlke K, Powell MA, Fader AN, Franklin GE, Lee LJ et al (2015) Postoperative radiation therapy for endometrial cancer: American society of clinical oncology clinical practice guideline endorsement of the american society for radiation oncology evidence-based guideline. J Clin Oncol 33:2908–2913

    Article  CAS  PubMed  Google Scholar 

  • Nikolopoulos GK, Bagos PG, Tsangaris I, Tsiara CG, Kopterides P, Vaiopoulos A et al (2014) The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis. Clin Chem Lab Med 52:937–950

    Article  CAS  PubMed  Google Scholar 

  • Rabi ZA, Todorović-Raković N, Vujasinović T, Milovanović J, Nikolić-Vukosavljević D (2015) Markers of progression and invasion in short term follow up of untreated breast cancer patients. Cancer Biomark 15:745–754

    Article  PubMed  Google Scholar 

  • Said JM, Tsui R, Borg AJ, Higgins JR, Moses EK, Walker SP et al (2012) The PAI-1 4G/5G polymorphism is not associated with an increased risk of adverse pregnancy outcome in asymptomatic nulliparous women. J Thromb Haemost 10:881–886

    Article  CAS  PubMed  Google Scholar 

  • Su CK, Yeh KT, Yeh CB, Wang PH, Ho ES, Chou MC et al (2011) Genetic polymorphism of the plasminogen activator inhibitor-1 is associated with an increased risk of endometrial cancer. J Surg Oncol 104:755–759

    Article  CAS  PubMed  Google Scholar 

  • Taponeco F, Curcio C, Giuntini A, Nardini V, Fornaciari G, Artini PG et al (2001) Expression and prognostic significance of urokinase and plasminogen activator inhibitor type-1 in endometrial hyperplasia and cancer. J Exp Clin Cancer Res 20:239–246

    CAS  PubMed  Google Scholar 

  • Wang S, Cao Q, Wang X, Li B, Tang M, Yuan W et al (2013) PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis. PLoS ONE 8:e56797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu Q, Zhao Z (2002) Inhibition of PAI-1: a new anti-thrombotic approach. Current Drug Targets Cardiovasc Haematol Disord 2:27–42

    Article  CAS  Google Scholar 

  • Wyganowska-Świątkowska M, Jankun J (2015) Plasminogen activation system in oral cancer: relevance in prognosis and therapy (review). Int J Oncol 47:16–24

    PubMed  Google Scholar 

  • Xu X, Xie Y, Lin Y, Xu X, Zhu Y, Mao Y et al (2012) PAI-1 promoter 4G/5G polymorphism (rs1799768) contributes to tumor susceptibility: evidence from meta-analysis. Exp Ther Med 4:1127–1133

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Medicine, Department of Medical Genetics, Cumhuriyet University, 58140, Sivas, Turkey

    Malik Ejder Yıldırım & Hande Küçük Kurtulgan

  2. Faculty of Medicine, Department of Obstetrics and Gynecology, Cumhuriyet University, 58140, Sivas, Turkey

    Savas Karakuş

  3. Faculty of Health Sciences, Department of Nutrition and Dietetic, Erzincan University, 24030, Erzincan, Turkey

    Hasan Kılıçgün

  4. Faculty of Medicine, Department of Medical Biochemistry, Cumhuriyet University, 58140, Sivas, Turkey

    Serpil Erşan & Sevtap Bakır

Authors
  1. Malik Ejder Yıldırım
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Savas Karakuş
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hande Küçük Kurtulgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hasan Kılıçgün
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Serpil Erşan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sevtap Bakır
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hasan Kılıçgün.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yıldırım, M.E., Karakuş, S., Kurtulgan, H.K. et al. The Association of Plasminogen Activator Inhibitor Type 1 (PAI-1) Level and PAI-1 4G/5G Gene Polymorphism with the Formation and the Grade of Endometrial Cancer. Biochem Genet 55, 314–321 (2017). https://doi.org/10.1007/s10528-017-9796-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-017-9796-7

Keywords

Search

Navigation